Down-Regulation of the Monocarboxylate Transporter 1 Is Involved in Butyrate Deficiency During Intestinal Inflammation

Thibault, Ronan; Coppet, Pierre de; Daly, Kristian; Bourreille, Arnaud; Cuff, Mark A.; Bonnet, Christian; Mosnier, Jean‐François; Galmiche, Jean–Paul; Shirazi-Beechey, Soraya P.; Segain, Jean–Pierre

doi:10.1053/j.gastro.2007.08.041

Cited by 178 publications

(162 citation statements)

References 27 publications

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“…This may provide an interesting link between impaired protective effects of butyrate on the colonic epithelium and pro-inflammatory conditions in the colon of pigs fed high-protein diets. In fact, the higher butyrate concentration in the colonic lumen of piglets fed a (16) .…”

Section: Discussionmentioning

confidence: 93%

Down-regulation of monocarboxylate transporter 1 (MCT1) gene expression in the colon of piglets is linked to bacterial protein fermentation and pro-inflammatory cytokine-mediated signalling

et al. 2015

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The present study investigated the influence of bacterial metabolites on monocarboxylate transporter 1 (MCT1) expression in pigs using in vivo, ex vivo and in vitro approaches. Piglets (n 24) were fed high-protein (26 %) or low-protein (18 %) diets with or without fermentable carbohydrates. Colonic digesta samples were analysed for a broad range of bacterial metabolites. The expression of MCT1, TNF-a, interferon g (IFN-g) and IL-8 was determined in colonic tissue. The expression of MCT1 was lower and of TNF-a and IL-8 was higher with high-protein diets (P, 0·05). MCT1 expression was positively correlated with L-lactate, whereas negatively correlated with NH 3 and putrescine (P,0·05). The expression of IL-8 and TNF-a was negatively correlated with L-lactate and positively correlated with NH 3 and putrescine, whereas the expression of IFN-g was positively correlated with histamine and 4-ethylphenol (P,0·05). Subsequently, porcine colonic tissue and Caco-2 cells were incubated with Na-butyrate, NH 4 Cl or TNF-a as selected bacterial metabolites or mediators of inflammation. Colonic MCT1 expression was higher after incubation with Na-butyrate (P,0·05) and lower after incubation with NH 4 Cl or TNF-a (P,0·05). Incubation of Caco-2 cells with increasing concentrations of these metabolites confirmed the up-regulation of MCT1 expression by Na-butyrate (linear, P, 0·05) and down-regulation by TNF-a and NH 4 Cl (linear, P,0·05). The high-protein diet decreased the expression of MCT1 in the colon of pigs, which appears to be linked to NH 3 -and TNF-a-mediated signalling.

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Section: Discussionmentioning

confidence: 93%

Down-regulation of monocarboxylate transporter 1 (MCT1) gene expression in the colon of piglets is linked to bacterial protein fermentation and pro-inflammatory cytokine-mediated signalling

et al. 2015

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“…The impaired butyrate metabolism could be due to luminal compounds interfering with butyrate metabolism, changes in luminal butyrate concentrations or pH, and defects in β-oxidation or butyrate transport (Thibault et al, 2010). Butyrate deficiency develops from decreased uptake of butyrate by the inflamed mucosa through down-regulation of the monocarboxylate transporter 1 (Thibault et al, 2007). The intracellular butyrate deficiency in colonocytes may decrease its protective effects against UC.…”

Section: Discussionmentioning

confidence: 99%

Intraperitoneal administration of butyrate prevents the severity of acetic acid colitis in rats

Malago

Sangu²

2015

J. Zhejiang Univ. Sci. B

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Intrarectal infusion of butyrate improves colorectal disorders including ulcerative colitis (UC). However, it is not established whether systemically administered butyrate benefits such patients. The current study aimed at exploring and comparing the potential of intraperitoneally, intrarectally, and orally administered butyrate against acetic acid (AA)-induced UC in rats. Intrarectal administration of 2 ml of 50% AA was done after or without prior treatment of rats for 7 consecutive days with 100 mg/kg sodium butyrate (SB) intraperitoneally, intrarectally, or orally. Rats were sacrificed after 48 h of AA-treatment. Subsequently, colon sections were processed routinely for histopathological examination. We clinically observed diarrhea, loose stools, and hemoccult-positive stools, and histologically, epithelial loss and ulceration, crypt damage, goblet cell depletion, hemorrhage, and mucosal infiltration of inflammatory cells. The changes were significantly reduced by intraperitoneal, intrarectal, or oral butyrate, with intraperitoneal butyrate exhibiting the highest potency. It is concluded that intraperitoneal administration of butyrate abrogates the lesions of AA-induced UC and its potency surpasses that of intrarectal or oral butyrate.

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“…For instance, impaired butyrate oxidation has been associated with active mucosal inflammation. Apart from reduced butyrate oxidation itself, impaired butyrate uptake, most likely as a consequence of decreased MCT1 expression, was found in patients with active ulcerative colitis 45, 46. Moreover, density analyses from an open access genomewide association studies database revealed a dense cluster of associations for SLC16A7 (encoding for MCT2) variants with Crohn disease and high‐density lipoprotein (HDL) cholesterol levels, although functional validation is completely missing so far 47…”

Section: Mcts In Other Diseasesmentioning

confidence: 99%

Clinical and Functional Relevance of the Monocarboxylate Transporter Family in Disease Pathophysiology and Drug Therapy

Fisel

Schaeffeler

Schwab

2018

Clinical Translational Sci

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The solute carrier (SLC) SLC16 gene family comprises 14 members and encodes for monocarboxylate transporters (MCTs), which mediate the absorption and distribution of monocarboxylic compounds across plasma membranes. As the knowledge about their physiological function, activity, and regulation increases, their involvement and contribution to cancer and other diseases become increasingly evident. Moreover, promising opportunities for therapeutic interventions by directly targeting their endogenous functions or by exploiting their ability to deliver drugs to specific organ sites emerge.

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Down-Regulation of the Monocarboxylate Transporter 1 Is Involved in Butyrate Deficiency During Intestinal Inflammation

Cited by 178 publications

References 27 publications

Down-regulation of monocarboxylate transporter 1 (MCT1) gene expression in the colon of piglets is linked to bacterial protein fermentation and pro-inflammatory cytokine-mediated signalling

Down-regulation of monocarboxylate transporter 1 (MCT1) gene expression in the colon of piglets is linked to bacterial protein fermentation and pro-inflammatory cytokine-mediated signalling

Intraperitoneal administration of butyrate prevents the severity of acetic acid colitis in rats

Clinical and Functional Relevance of the Monocarboxylate Transporter Family in Disease Pathophysiology and Drug Therapy

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